This study was designed to use different antioxidant as hydrocortisone, vitamin C, vitamin E, and combination of them against experimental intestine ischemia-reperfusion (IR) for decrease free radical damage in soft tissue. Thirty adult male Wistar rats were selected randomly and divided into six equal groups. Group Sham: intact group, group control: IR group with 45 min of ischemia followed by 1 h of reperfusion, group vitamin C: IR plus vitamin C (50 mg/kg, IV) treatment immediately after reperfusion, group vitamin E: IR plus vitamin E (20 mg/kg, IM) treatment 15 min before reperfusion, group hydrocortisone: IR plus hydrocortisone (50 mg/kg, IV) treatment immediately after reperfusion and group combination: IR plus combination of vitamin C, E, and hydrocortisone. Ischemia was induced by clamping the supraciliac artery. In the end of time of reperfusion, the proximal segment of jejunum was collected as a tissue specimen for histopathologic examination. In histopathological study, severe damage was detected in intestinal mucosa to all control and treatment groups, and histopathologic score was significantly decreased in the treatment groups. Analysis of the histopathological results showed that in the all treatment groups, the intestinal mucosal injury was decreased compared to the control group and in the combination group, the protection was better than the other treatment groups. The results showed simultaneous administration of vitamin C, E, and hydrocortisone combination before reperfusion of blood flow to the ischemic tissue could improve the deleterious effects of IR injuries in intestinal mucosa.